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CDS2 expression regulates de novo phosphatidic acid synthesis. CDS2 的表达调控 PA 的从头合成。
IF 4.4 3区 生物学
Biochemical Journal Pub Date : 2024-10-16 DOI: 10.1042/BCJ20240456
Daniel M Collins, Vishnu Janardan, David Barneda, Karen E Anderson, Izabella Niewczas, Diane Taylor, Danye Qiu, Henning J Jessen, Andrea F Lopez-Clavijo, Simon Walker, Padinjat Raghu, Jonathan Clark, Len R Stephens, Phillip T Hawkins
{"title":"CDS2 expression regulates de novo phosphatidic acid synthesis.","authors":"Daniel M Collins, Vishnu Janardan, David Barneda, Karen E Anderson, Izabella Niewczas, Diane Taylor, Danye Qiu, Henning J Jessen, Andrea F Lopez-Clavijo, Simon Walker, Padinjat Raghu, Jonathan Clark, Len R Stephens, Phillip T Hawkins","doi":"10.1042/BCJ20240456","DOIUrl":"10.1042/BCJ20240456","url":null,"abstract":"<p><p>CDS enzymes (CDS1 and 2 in mammals) convert phosphatidic acid (PA) to CDP-DG, an essential intermediate in the de novo synthesis of PI. Genetic deletion of CDS2 in primary mouse macrophages resulted in only modest changes in the steady-state levels of major phospholipid species, including PI, but substantial increases in several species of PA, CDP-DG, DG and TG. Stable isotope labelling experiments employing both 13C6- and 13C6D7-glucose revealed loss of CDS2 resulted in a minimal reduction in the rate of de novo PI synthesis but a substantial increase in the rate of de novo PA synthesis from G3P, derived from DHAP via glycolysis. This increased synthesis of PA provides a potential explanation for normal basal PI synthesis in the face of reduced CDS capacity (via increased provision of substrate to CDS1) and increased synthesis of DG and TG (via increased provision of substrate to LIPINs). However, under conditions of sustained GPCR-stimulation of PLC, CDS2-deficient macrophages were unable to maintain enhanced rates of PI synthesis via the 'PI cycle', leading to a substantial loss of PI. CDS2-deficient macrophages also exhibited significant defects in calcium homeostasis which were unrelated to the activation of PLC and thus probably an indirect effect of increased basal PA. These experiments reveal that an important homeostatic response in mammalian cells to a reduction in CDS capacity is increased de novo synthesis of PA, likely related to maintaining normal levels of PI, and provides a new interpretation of previous work describing pleiotropic effects of CDS2 deletion on lipid metabolism/signalling.</p>","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Permeation mechanisms of hydrogen peroxide and water through Plasma Membrane Intrinsic Protein aquaporins. 过氧化氢和水通过质膜固有蛋白(PIP)水蒸发蛋白的渗透机制。
IF 4.4 3区 生物学
Biochemical Journal Pub Date : 2024-10-02 DOI: 10.1042/BCJ20240310
Jonathan Chevriau, Gerardo Zerbetto De Palma, Cintia Jozefkowicz, Victoria Vitali, Agustina Canessa Fortuna, Nicolas Ayub, Gabriela Soto, Gerd Patrick Bienert, Ari Zeida, Karina Alleva
{"title":"Permeation mechanisms of hydrogen peroxide and water through Plasma Membrane Intrinsic Protein aquaporins.","authors":"Jonathan Chevriau, Gerardo Zerbetto De Palma, Cintia Jozefkowicz, Victoria Vitali, Agustina Canessa Fortuna, Nicolas Ayub, Gabriela Soto, Gerd Patrick Bienert, Ari Zeida, Karina Alleva","doi":"10.1042/BCJ20240310","DOIUrl":"10.1042/BCJ20240310","url":null,"abstract":"<p><p>Hydrogen peroxide (H2O2) transport by aquaporins (AQP) is a critical feature for cellular redox signaling. However, the H2O2 permeation mechanism through these channels remains poorly understood. Through functional assays, two Plasma membrane Intrinsic Protein (PIP) AQP from Medicago truncatula, MtPIP2;2 and MtPIP2;3 have been identified as pH-gated channels capable of facilitating the permeation of both water (H2O) and H2O2. Employing a combination of unbiased and enhanced sampling molecular dynamics simulations, we investigated the key barriers and translocation mechanisms governing H2O2 permeation through these AQP in both open and closed conformational states. Our findings reveal that both H2O and H2O2 encounter their primary permeation barrier within the selectivity filter (SF) region of MtPIP2;3. In addition to the SF barrier, a second energetic barrier at the NPA (asparagine-proline-alanine) region that is more restrictive for the passage of H2O2 than for H2O, was found. This behavior can be attributed to a dissimilar geometric arrangement and hydrogen bonding profile between both molecules in this area. Collectively, these findings suggest mechanistic heterogeneity in H2O and H2O2 permeation through PIPs.</p>","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances in the cell biology of the trafficking and processing of amyloid precursor protein: impact of familial Alzheimer's disease mutations. 淀粉样前体蛋白贩运和处理的细胞生物学研究进展:家族性阿尔茨海默病突变的影响。
IF 4.1 3区 生物学
Biochemical Journal Pub Date : 2024-10-02 DOI: 10.1042/bcj20240056
Jingqi Wang,Lou Fourriere,Paul A Gleeson
{"title":"Advances in the cell biology of the trafficking and processing of amyloid precursor protein: impact of familial Alzheimer's disease mutations.","authors":"Jingqi Wang,Lou Fourriere,Paul A Gleeson","doi":"10.1042/bcj20240056","DOIUrl":"https://doi.org/10.1042/bcj20240056","url":null,"abstract":"The production of neurotoxic amyloid-β peptides (Aβ) is central to the initiation and progression of Alzheimer's disease (AD) and involves sequential cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. APP and the secretases are transmembrane proteins and their co-localisation in the same membrane-bound sub-compartment is necessary for APP cleavage. The intracellular trafficking of APP and the β-secretase, BACE1, is critical in regulating APP processing and Aβ production and has been studied in several cellular systems. Here, we summarise the intracellular distribution and transport of APP and its secretases, and the intracellular location for APP cleavage in non-polarised cells and neuronal models. In addition, we review recent advances on the potential impact of familial AD mutations on APP trafficking and processing. This is critical information in understanding the molecular mechanisms of AD progression and in supporting the development of novel strategies for clinical treatment.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Retraction: Mechanism of short-term ERK activation by electromagnetic fields at mobile phone frequencies. 撤回:手机频率电磁场短期激活ERK的机制
IF 4.1 3区 生物学
Biochemical Journal Pub Date : 2024-10-02 DOI: 10.1042/bj20061653_ret
{"title":"Retraction: Mechanism of short-term ERK activation by electromagnetic fields at mobile phone frequencies.","authors":"","doi":"10.1042/bj20061653_ret","DOIUrl":"https://doi.org/10.1042/bj20061653_ret","url":null,"abstract":"","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Novel phosphatidylinositol flippases contribute to phosphoinositide homeostasis in the plasma membrane. 新型磷脂酰肌醇翻转酶有助于质膜中磷脂酰肌醇的平衡。
IF 4.4 3区 生物学
Biochemical Journal Pub Date : 2024-09-18 DOI: 10.1042/BCJ20240223
Yumeka Muranaka, Ryo Shigetomi, Yugo Iwasaki, Asuka Hamamoto, Kazuhisa Nakayama, Hiroyuki Takatsu, Hye-Won Shin
{"title":"Novel phosphatidylinositol flippases contribute to phosphoinositide homeostasis in the plasma membrane.","authors":"Yumeka Muranaka, Ryo Shigetomi, Yugo Iwasaki, Asuka Hamamoto, Kazuhisa Nakayama, Hiroyuki Takatsu, Hye-Won Shin","doi":"10.1042/BCJ20240223","DOIUrl":"https://doi.org/10.1042/BCJ20240223","url":null,"abstract":"<p><p>Phosphatidylinositol is a precursor of various phosphoinositides, which play crucial roles in intracellular signaling and membrane dynamics and have impact on diverse aspects of cell physiology. Phosphoinositide synthesis and turnover occur in the cytoplasmic leaflet of the organellar and plasma membranes. P4-ATPases (lipid flippases) are responsible for translocating membrane lipids from the exoplasmic (luminal) to the cytoplasmic leaflet, thereby regulating membrane asymmetry. However, the mechanism underlying phosphatidylinositol translocation across cellular membranes remains elusive. Here, we discovered that the phosphatidylcholine flippases ATP8B1, ATP8B2, and ATP10A can also translocate phosphatidylinositol at the plasma membrane. To explore the function of these phosphatidylinositol flippases, we used cells depleted of CDC50A, a protein necessary for P4-ATPase function and ATP8B1 and ATP8B2, which express in HeLa cells. Upon activation of the Gq-coupled receptor, depletion of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] was accelerated in CDC50A knockout (KO) and ATP8B1/8B2 double KO cells compared with control cells, suggesting a decrease in PtdIns(4,5)P2 levels within the plasma membrane of the KO cells upon stimulation. These findings highlight the important role of P4-ATPases in maintaining phosphoinositide homeostasis and suggest a mechanism for asymmetry of phosphatidylinositol in the cytoplasmic leaflet of the plasma membrane.</p>","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CARD14 signalosome formation is associated with its endosomal relocation and mTORC1-induced keratinocyte proliferation. CARD14 信号体的形成与其内表皮迁移和 mTORC1 诱导的角膜细胞增殖有关。
IF 4.4 3区 生物学
Biochemical Journal Pub Date : 2024-09-18 DOI: 10.1042/BCJ20240058
Paul A O'Sullivan, Aigerim Aidarova, Inna S Afonina, Joan Manils, Teresa L M Thurston, Rachael Instrell, Michael Howell, Stefan Boeing, Sashini Ranawana, Melanie B Herpels, Riwia Chetian, Matilda Bassa, Helen Flynn, David Frith, Ambrosius P Snijders, Ashleigh Howes, Rudi Beyaert, Anne M Bowcock, Steven C Ley
{"title":"CARD14 signalosome formation is associated with its endosomal relocation and mTORC1-induced keratinocyte proliferation.","authors":"Paul A O'Sullivan, Aigerim Aidarova, Inna S Afonina, Joan Manils, Teresa L M Thurston, Rachael Instrell, Michael Howell, Stefan Boeing, Sashini Ranawana, Melanie B Herpels, Riwia Chetian, Matilda Bassa, Helen Flynn, David Frith, Ambrosius P Snijders, Ashleigh Howes, Rudi Beyaert, Anne M Bowcock, Steven C Ley","doi":"10.1042/BCJ20240058","DOIUrl":"10.1042/BCJ20240058","url":null,"abstract":"<p><p>Rare mutations in CARD14 promote psoriasis by inducing CARD14-BCL10-MALT1 complexes that activate NF-κB and MAP kinases. Here, the downstream signalling mechanism of the highly penetrant CARD14E138A alteration is described. In addition to BCL10 and MALT1, CARD14E138A associated with several proteins important in innate immune signalling. Interactions with M1-specific ubiquitin E3 ligase HOIP, and K63-specific ubiquitin E3 ligase TRAF6 promoted BCL10 ubiquitination and were essential for NF-κB and MAP kinase activation. In contrast, the ubiquitin binding proteins A20 and ABIN1, both genetically associated with psoriasis development, negatively regulated signalling by inducing CARD14E138A turnover. CARD14E138A localized to early endosomes and was associated with the AP2 adaptor complex. AP2 function was required for CARD14E138A activation of mTOR complex 1 (mTORC1), which stimulated keratinocyte metabolism, but not for NF-κB nor MAP kinase activation. Furthermore, rapamycin ameliorated CARD14E138A-induced keratinocyte proliferation and epidermal acanthosis in mice, suggesting that blocking mTORC1 may be therapeutically beneficial in CARD14-dependent psoriasis.</p>","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Using a cellulose-complementary oligosaccharide as a tool to probe exposed cellulosic surfaces in cotton fibres and growing plant cell walls. 以纤维素互补寡糖为工具,探测棉纤维和生长植物细胞壁中暴露的纤维素表面。
IF 4.4 3区 生物学
Biochemical Journal Pub Date : 2024-09-18 DOI: 10.1042/BCJ20240296
Mahnoor Imran, Lenka Franková, Uzma Qaisar, Stephen C Fry
{"title":"Using a cellulose-complementary oligosaccharide as a tool to probe exposed cellulosic surfaces in cotton fibres and growing plant cell walls.","authors":"Mahnoor Imran, Lenka Franková, Uzma Qaisar, Stephen C Fry","doi":"10.1042/BCJ20240296","DOIUrl":"10.1042/BCJ20240296","url":null,"abstract":"<p><p>Cellulosic microfibrils in plant cell walls are largely ensheathed and probably tethered by hydrogen-bonded hemicelluloses. Ensheathing may vary developmentally as hemicelluloses are peeled to enable cell expansion. We characterised a simple method to quantify ensheathed versus naked cellulosic surfaces based on the ability to adsorb a radiolabelled 'cellulose-complementary oligosaccharide', [3H]cellopentaitol. Filter-paper (cellulose) adsorbed 40% and >80% of aqueous 5 nM [3H]cellopentaitol within ∼1 and ∼20 h respectively. When [3H]cellopentaitol was rapidly dried onto filter-paper, ∼50% of it was desorbable by water, whereas after ∼1 day annealing in aqueous medium the adsorption became too strong to be reversible in water. 'Strongly' adsorbed [3H]cellopentaitol was, however, ∼98% desorbed by 6 M NaOH, ∼50% by 0.2 M cellobiose, and ∼30% by 8 M urea, indicating a role for hydrogen-bonding reinforced by complementarity of shape. Gradual adsorption was promoted by kosmotropes (1.4 M Na2SO4 or 30% methanol), and inhibited by chaotropes (8 M urea), supporting a role for hydrogen-bonding. [3H]Cellopentaitol adsorption was strongly competed by non-radioactive cello-oligosaccharides (Cell2-6), the IC50 (half-inhibitory concentration) being highly size-dependent: Cell2, ∼70 mM; Cell3, ∼7 mM; and Cell4-6, ∼0.05 mM. Malto-oligosaccharides (400 mM) had no effect, confirming the role of complementarity. The quantity of adsorbed [3H]cellopentaitol was proportional to mass of cellulose. Of seven cottons tested, wild-type Gossypium arboreum fibres were least capable of adsorbing [3H]cellopentaitol, indicating ensheathment of their microfibrillar surfaces, confirmed by their resistance to cellulase digestion, and potentially attributable to a high glucuronoarabinoxylan content. In conclusion, [3H]cellopentaitol adsorption is a simple, sensitive and quantitative way of titrating 'naked' cellulose surfaces.</p>","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The pro-drug C13 activates AMPK by two distinct mechanisms. 原药 C13 通过两种不同的机制激活 AMPK。
IF 4.4 3区 生物学
Biochemical Journal Pub Date : 2024-09-18 DOI: 10.1042/BCJ20240425
Jordana B Freemantle, Dinesh Shah, Dylan M Lynch, Alessio Ciulli, Harinder S Hundal, D Grahame Hardie
{"title":"The pro-drug C13 activates AMPK by two distinct mechanisms.","authors":"Jordana B Freemantle, Dinesh Shah, Dylan M Lynch, Alessio Ciulli, Harinder S Hundal, D Grahame Hardie","doi":"10.1042/BCJ20240425","DOIUrl":"10.1042/BCJ20240425","url":null,"abstract":"<p><p>The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that is expressed in almost all eukaryotic cells. In the canonical activation mechanism, it is activated by increases in AMP:ATP and ADP:ATP ratios that signify declining cellular energy status. Once activated, AMPK phosphorylates numerous targets that promote catabolic pathways generating ATP, while inhibiting anabolic and other processes that consume ATP, thus acting to restore energy homeostasis. Pharmacological agents that activate AMPK have been useful in identifying downstream targets and have potential as drugs for treatment of metabolic disorders such as Type 2 diabetes and non-alcoholic fatty liver disease. One such agent is C13, a pro-drug with a phosphonate bis(isobutyryloxymethyl) ester moiety, with the isobutyryloxymethyl groups increasing membrane permeability. Following cellular uptake, C13 is cleaved to release C2, an AMP analogue and potent AMPK activator that is specific for complexes containing the α1 (but not the α2) catalytic subunit isoform. This has previously been assumed to be the sole mechanism by which C13 activates AMPK, with potential roles for the isobutyryloxymethyl groups being ignored. We now report that, following cleavage from C13, these protective groups are metabolized to formaldehyde, an agent that inhibits mitochondrial function and increases cellular AMP:ATP ratios, thus providing additional AMPK activation by the canonical mechanism.</p>","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Proteolysis of tau by granzyme A in tauopathies generates fragments that are aggregation prone. 在牛头脑病中,颗粒酶 A 对牛头脑蛋白的蛋白水解产生易聚集的片段。
IF 4.4 3区 生物学
Biochemical Journal Pub Date : 2024-09-18 DOI: 10.1042/BCJ20240007
James P Quinn, Kate Fisher, Nicola Corbett, Stacey Warwood, David Knight, Katherine A B Kellett, Nigel M Hooper
{"title":"Proteolysis of tau by granzyme A in tauopathies generates fragments that are aggregation prone.","authors":"James P Quinn, Kate Fisher, Nicola Corbett, Stacey Warwood, David Knight, Katherine A B Kellett, Nigel M Hooper","doi":"10.1042/BCJ20240007","DOIUrl":"10.1042/BCJ20240007","url":null,"abstract":"<p><p>Tauopathies, including Alzheimer's disease, corticobasal degeneration and progressive supranuclear palsy, are characterised by the aggregation of tau into insoluble neurofibrillary tangles in the brain. Tau is subject to a range of post-translational modifications, including proteolysis, that can promote its aggregation. Neuroinflammation is a hallmark of tauopathies and evidence is growing for a role of CD8+ T cells in disease pathogenesis. CD8+ T cells release granzyme proteases but what role these proteases play in neuronal dysfunction is currently lacking. Here, we identified that granzyme A (GzmA) is present in brain tissue and proteolytically cleaves tau. Mass spectrometric analysis of tau fragments produced on digestion of tau with GzmA identified three cleavage sites at R194-S195, R209-S210 and K240-S241. Mutation of the critical Arg or Lys residues at the cleavage sites in tau or chemical inhibition of GzmA blocked the proteolysis of tau by GzmA. Development of a semi-targeted mass spectrometry approach identified peptides in tauopathy brain tissue corresponding to proteolysis by GzmA at R209-S210 and K240-S241 in tau. When expressed in cells the GzmA-cleaved C-terminal fragments of tau were highly phosphorylated and aggregated upon incubation of the cells with tauopathy brain seed. The C-terminal fragment tau195-441 was able to transfer between cells and promote aggregation of tau in acceptor cells, indicating the propensity for such tau fragments to propagate between cells. Collectively, these results raise the possibility that GzmA, released from infiltrating cytotoxic CD8+ T cells, proteolytically cleaves tau into fragments that may contribute to its pathological properties in tauopathies.</p>","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A hybrid biosynthetic-catabolic pathway for norspermidine production. 生产去甲金丝桃苷的生物合成-代谢混合途径
IF 4.4 3区 生物学
Biochemical Journal Pub Date : 2024-09-18 DOI: 10.1042/BCJ20240411
Bin Li, Jue Liang, Margaret A Phillips, Anthony J Michael
{"title":"A hybrid biosynthetic-catabolic pathway for norspermidine production.","authors":"Bin Li, Jue Liang, Margaret A Phillips, Anthony J Michael","doi":"10.1042/BCJ20240411","DOIUrl":"10.1042/BCJ20240411","url":null,"abstract":"<p><p>The only known pathway for biosynthesis of the polyamine norspermidine starts from aspartate β-semialdehyde to form the diamine 1,3-diaminopropane, which is then converted to norspermidine via a carboxynorspermidine intermediate. This pathway is found primarily in the Vibrionales order of the γ-Proteobacteria. However, norspermidine is also found in other species of bacteria and archaea, and in diverse single-celled eukaryotes, chlorophyte algae and plants that do not encode the known norspermidine biosynthetic pathway. We reasoned that products of polyamine catabolism could be an alternative route to norspermidine production. 1,3-diaminopropane is formed from terminal catabolism of spermine and spermidine, and norspermidine can be formed from catabolism of thermospermine. We found that the single-celled chlorophyte alga Chlamydomonas reinhardtii thermospermine synthase (CrACL5) did not aminopropylate exogenously-derived 1,3-diaminopropane efficiently when expressed in Escherichia coli. In contrast, it completely converted all E. coli native spermidine to thermospermine. Co-expression in E. coli of the polyamine oxidase 5 from lycophyte plant Selaginella lepidophylla (SelPAO5), together with the CrACL5 thermospermine synthase, converted almost all thermospermine to norspermidine. Although CrACL5 was efficient at aminopropylating norspermidine to form tetraamine norspermine, SelPAO5 oxidizes norspermine back to norspermidine, with the balance of flux being inclined fully to norspermine oxidation. The steady-state polyamine content of E. coli co-expressing thermospermine synthase CrACL5 and polyamine oxidase SelPAO5 was an almost total replacement of spermidine by norspermidine. We have recapitulated a potential hybrid biosynthetic-catabolic pathway for norspermidine production in E. coli, which could explain norspermidine accumulation in species that do not encode the known aspartate β-semialdehyde-dependent pathway.</p>","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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